DESCRIPTION (provided by investigator): Schizophrenia is increasingly viewed as a neurodevelopmental disorder, but prospective studies of the etiology and premorbid manifestations are hampered by the lack of a homogeneous study population. Chromosome 22q11 deletion syndrome (22q11DS) is an autosomal dominant microdeletion syndrome, associated with congenital abnormalities, cognitive impairment and a markedly increased incidence (40%) of schizophrenia and other major psychoses in late adolescence/adulthood. Due to the relatively recent discovery of the relationship between 22q11DS and psychosis - there is little knowledge regarding the pathogenesis and the clinical course of psychoses in these individuals. We hypothesize that a subset of nonpsychotic children with 22q11DS will exhibit elevated rates of schizophrenic-like cognitive/behavioral/neurodevelopmental deficits. Theoretical evidence suggests that such deficits in nonpsychotic individuals predict a heightened risk of psychosis in late adolescence/adulthood. We propose a cross-sectional study on 35 children with 22q11DS and 35 age and gender matched healthy control subjects. The study will assess medical status, pedigree data, neurodevelopmental history, intellectual ability, psychometric/biobehavioral/neurocognitive measures of risk for schizophrenia and structural brain abnormalities by morphometric analyses. Our preliminary data on 13 children with 22q11DS and 13 control subjects indicate that children with 22q11DS exhibit higher rates of deficits in sustained attention and executive functioning. On brain MRI, midline deviations such as cavum septum pellucidum/vergae are common (7/13 patients). The corpus callosum (CC) area and the area of the isthmus of the CC are increased in the 22q11DS patients. On correlating the neuropsychological and MRI findings, increasing size of the genu of the CC is associated with decreasing verbal IQ and verbal learning and memory. Thus, our findings are suggestive of increased rates of neuropsychological and neuroanatomical abnormalities in children with 22q11DS. Further characterization of these abnormalities in the proposed cross-sectional study will form the basis of a future longitudinal study of risk for schizophrenia and other psychoses in these children. The successful characterization of schizophrenic-like deficits should facilitate the identification of individuals at high-risk. The strengths of the proposed study are that we would examine vulnerability associated with a specific genetic abnormality, integrate measures from a variety of medical and psychological domains, and ascertain a sample for longitudinal study of risk for developing schizophrenia and related disorders.